Spinal Muscular Atrophy (SMA) is an often-fatal genetic disorder resulting from the loss of the Survival Motor Neuron (SMN) protein encoded by the Survival Motor Neuron (SMN) gene. The SMN genes, SMN1 and SMN2, are located on chromosome 5 and SMA is caused by the loss of SMN1 from both chromosomes. SMN2, while being almost identical to SMN1, is less effective at making the SMN protein. The severity of SMA is affected by the efficiency at which SMN2, of which there are several copies, produces the SMN protein.
SMA can be classified by the severity of the disorder. Infantile SMA (SMA type 1 or Werdnig-Hoffmann disease) affects infants from the ages of 0-6 months and is the most severe. It causes the affected child to be unable to maintain an independent sitting position. Intermediate SMA (SMA type 2) affects children from the ages of 7-18 months. Children with SMA type 2 are never able to stand and walk, but are able to maintain a sitting position at least some time in their life. The onset of weakness is usually recognized some time between 6 and 18 months. Juvenile SMA (SMA type 3 or Kugelberg-Welander disease) affects children generally older than 18 months. These children are able to walk at some time. Adult SMA (SMA type 4) usually causes weakness beginning in late adolescence in the tongue, hands, or feet, and it progresses to other areas of the body. The course of disease is much slower and has little or no impact on life expectancy. Typically, the earlier the onset of the disease, the shorter the lifespan of the victim. Infants with the severe form of SMA frequently succumb to respiratory disease due to weakness of the muscles that support breathing. Children with milder forms of SMA naturally live much longer although they may need extensive medical support, especially those at the more severe end of the spectrum.
Although gene replacement strategies are being tested in animals, current treatment for SMA consists of prevention and management of the secondary effect of chronic motor unit loss. Currently, there are no drug therapies available for the treatment or prevention of SMA.